• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3747-3752
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• 2014

Background: Gallbladder carcinoma (GBC) is the most common carcinoma of the biliary system. Among its research models, orthotopic xenograft models, important research tools, have been rarely reported in the literature however. Aim: To explore establishment of an orthotopic xenograft model and to evaluate the advantage and disadvantage as compared with other models. Materials and Methods: Subcutaneous xenograft and orthotopic xenograft models of gallbladder carcinoma in nude mice were established and compared with human gallbladder carcinomas. Results: For the orthotopic xenograft model and clinical gallbladder carcinomas, the lymph node metastatic rates were 69.2% and 53.3% (p>0.05); ascites generation rates, 38.5% and 11.7%(p<0.05); liver invasive rates, 100% and 61.7%(p<0.05); and lymphatic vessel densities (LVD), $10.4{\pm}3.02$ and $8.77{\pm}2.92$ (p>0.05), respectively. In the subcutaneous xenograft model, no evidence of ascites generation, lymph node metastasis and liver metastasis were found, and its LVD was lower ($4.56{\pm}1.53$, p<0.05). Conclusions: Compared with the subcutaneous xenograft model, the orthotopic xenograft model better simulates clinical gallbladder carcinoma in terms of metastasis and invasion, which may be attributed to the difference in microenvironment and LVD.

• Journal of Yeungnam Medical Science
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• v.32 no.2
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• pp.155-158
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• 2015

Lymphangioma is a congenital abnormality of the lymphatic system detected primarily in early childhood. There are rare reports of mediastinal lymphangioma in older adults. We hereby report on a 66-year-old female patient who underwent kidney transplantation 20 years previously and who developed pathologically confirmed solitary mediastinal lymphangioma 1 year ago. Chest radiography showed a mediastinal nodule, which was not observed 2 year previously, therefore she was referred to the pulmonary division. She had no symptoms, and chest computed tomography demonstrated a 25-mm, well-defined, low-density nodule located at the anterior mediastinum. The size of the nodule had increased from 25 mm to 34 mm 1 year later, and it was completely resected via video-assisted thoracic surgery. The histological diagnosis was cystic lymphangioma. Therefore, we recommend that clinicians consider cystic lymphangioma as a possible diagnosis even in older patients with a mediastinal cystic mass that shows progressive enlargement.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3551-3557
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• 2015

Background: Non-Hodgkin's lymphoma (NHL) is a heterogeneous type of neoplasm of the lymphatic system. To have a more accurate and early diagnosis we need to know signs, symptoms and complications of lymphoma in early stages besides pathology and immunohistochemistry. Materials and Methods: This prospective study included 110 cases of NHL that were followed since February 2012 till November 2013. Biopsies were taken from all the patients besides bone marrow study. Signs and symptoms were categorized into "B" symptoms, general, lymphadenopathy and extranodal involvement and we compared the frequencies by stage and grade. Results: Of 110 cases, 88.9% had B-cell and 11.1% T-cell type with mean age $48.5{\pm}18.6$ years. "B" symptoms and lymphadenopathy were more common in men. Cervical lymphadenopathy was the most common sign (44.8%). and hematologic, bone marrow, bone and neurologic lesions were the most common complications. All complications were more common in males. "B" symptoms were seen mostly in stage III, general signs and symptoms in stage IV, and lymphadenopathy in stage II. Intermediate grade was also the most common in all signs and symptoms. In this study 12 (10.9%) patients had relapse, with neurologic and bone marrow as the most common sites of tumor recurrence. Conclusions: There is a meaningful relationship between male gender for NHL and anemia that can be due in part to higher incidence of bone marrow involvement and stage IV disease in male cases. We also found a strong relationship between low grade NHL and age. On the other hand extranodal involvement is more common in female groups.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.3
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• pp.991-994
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• 2012

Objective: VEGF-C has recently been identified as a key molecule which is involved in tumor lymphangiogenesis. The aim of this research was to investigate the role of PARP-1 inhibition in the regulation of VEGF-C expression in CT26 cells. Methods: CT26 cells were treated with or without the PARP-1 inhibitor 5-aminoisoquinolinone (5-AIQ). The expression of PARP-1, NF-kB, and VEGF-C proteins in CT26 cells was measured by Western blot analysis and the VEGF-C mRNA level was determined by reverse transcription polymerase chain reaction (RT-PCR). CT26-secreted VEGF-C was detected by enzyme-linked immunosorbent assay (ELISA). Results: The results of Western blot analysis showed that the expression levels of PARP-1, NF-kB, and VEGF-C were reduced in 5-AIQ treated CT26 cells and the levels of VEGF-C mRNA in 5-AIQ treated CT26 were significantly lower than t in 5-AIQ-untreated cells (P<0.05). The concentrations of CT26-secreted VEGF-C were also dramatically decreased (P<0.05). Conclusion: Here, we provide evidence for the first time that PARP-1 inhibition dramatically reduces VEGF-C expression via the nuclear factor NF-kB signaling pathway. We therefore propose that PARP-1 inhibition has an anti-lymphangiogenic effect and may contribute to the prevention of metastatic dissemination via the lymphatic system.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.1 no.1
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• pp.62-73
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• 2015

We developed an evans blue-indocyanine green-$^{99m}Tc$-human serum albumin conjugate for sentinel lymph node mapping and we describe its unique potential usage for clinical implications. This conjugate has combined the strengths of visible blue dye, near-infrared fluorescence and radioisotope into one single conjugate without any additional weakness/disadvantage. All the components of evans blue-indocyanine green-$^{99m}Tc$-human serum albumin are safe and of low cost, and they have already been clinically used. This conjugate was stable in the serum, it showed a long retention time in the lymphatic system and the lymph nodes showed a much higher signal-to-noise ratio after the conjugate was injected intradermally into the paw of mice. Both the single-photon emission computed tomography and near-infrared fluorescent images of the mice were successfully obtained at the same time as the excised sentinel lymph nodes showed blue color. The visual color, near-infrared fluorescence and gamma ray from this agent could be complementary for each other in all the steps of sentinel lymph node sampling: exploring and planning sentinel lymph node before excision with visualization of the exact sentinel lymph node location during an operation. Therefore, the triple modal agent will possibly be very ideal for sentinel lymph node mapping because of the high signal-to-noise ratio for non-invasive imaging and its complementary multimodal nature, easy preparation and safety. It is promising for clinical applications and it may have great advantages over the traditional single modal methods.

• Korean Journal of Veterinary Research
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• v.44 no.2
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• pp.311-315
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• 2004

The detection of lymph node metastasis is an important step in tumor staging and is significant for therapy planning. It has been challenged to yield an appropriate image with diagnostic methods such as Magnetic Resonance (MR) and Computed Tomography (CT). Though CT has been used widely and accessed easily to show internal organs, it can hardly provide difference between lymph node and adjacent vessel or fat tissue. It has been well established that MR can reveal the subtle discrepancy within soft tissue. This study investigated the suitability of MR lymph node imaging without contrast enhancement by comparison of T1-weighted image (T1WI) and T2- weighted image (T2WI) in ten normal rabbits. According to the pulse sequence optimized from preliminary study, T1-weighted spin-echo (repetition time/echo time=400/12 ms) and T-2 weighted fast spin-echo (repetition time/echo time=3500/84 ms) images covering the hind limbs and pelvic region were acquired at 1.5 T. Two radiologists scrupulously evaluated the MR images in consensus. And signal intensity of lymph nodes was compared with that of adjacent fat. Statistical analysis showed that T1-weighted coronal image visualized the lymph nodes (iliac, superficial inguinal and popliteal lymph nodes) quickly and consistently rather than T2-weighted one. Conclusively, T1WI for evaluation of lymph nodes is moderately better than T2WI and appears to have potential for quick and sufficient mapping of the lymph nodes. In addition, this normal MR image of lymph nodes could be applied to further study for the evaluation of lymphatic system in abscess and tumor bearing animal model.

• Current Optics and Photonics
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• v.1 no.2
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• pp.132-137
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• 2017

To investigate the usefulness of optical coherence tomography (OCT) for imaging lymphedema, we directly compared it to other histological methods in a mouse model of lymphedema. We performed detailed imaging of the lymphedema lesion on a mouse tail. We imaged the mouse tail in vivo with OCT and created histopathological samples. We constructed a spectrometer-based OCT system using a fiber-optic Michelson interferometer. The light was directed to 50:50 couplers that split the light into reference and sample arms. Backscattered light from a reference mirror and the sample produced an interference fringe. An OCT image of the lymphedema model revealed an inflammatory reaction of the skin that was accompanied by edema, leading to an increase in the light attenuation in the dermal and subcutaneous layers. Similar to OCT image findings, histological biopsy showed an inflammatory response that involved edema, increased neutrophils in epidermis and subdermis, and lymphatic microvascular dilatation. Furthermore, the lymphedema model showed an increase in thickness of the dermis in both diagnostic studies. In the mouse tail model of lymphedema, OCT imaging showed very similar results to other histological examinations. OCT provides a quick and useful diagnostic imaging technique for lymphedema and is a valuable addition or complement to other noninvasive imaging tools.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.30 no.6
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• pp.529-539
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• 2008

Background and Purpose : Oral squamous cell carcinoma (OSCC) is one of the most aggressive tumors of the head and neck area. OSCC is known to preferentially metastasize via lymphatic system, and resulting cervical lymph node metastasis is the most reliable of treatment failure. But the biological mechanism of the regional nodal metastasis is not clear. So, we determined metastasis-related factors in orthotopic nude mouse models of OSCC. Experimental Design : Two cell lines-KB and YD-10B cells, established from human oral mucosal squamous cell carcinoma, were xenografted into the tissue space of athymic murine mouth floor. The mice were followed for tumor development and growth, the murine tumors were examined histopathologically for local invasion or regional or distant metastasis. Finally, we performed immunohistochemical assays with antiepithelial growth factor (EGF), EGF receptor (EGFR), phosphorylated EGFR (pEGFR), and anti-vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR)-2, phosphorylated VEGFR-2/3 (pVEGFR-2/3) antibodies. We also determined the microvessel density. Results : Transplantation of human OSCC tumor cells into the mouth floor successfully resulted in the formation of orthotopic tumors. KB cell line showed significantly higher tumor proliferation and higher nodal metastatic potential than YD-10B cell line. Furthermore, immunohistochemical staining demonstrated higher expression of EGFR/pEGFR, VEGF, and pVEGFR-2/3 as well as higher microvessel density in KB murine tumors than in YD-10B murine tumors. Conclusion : An orthotopic model of OSCC in athymic mice was established which copies the cervical lymph nodal metastasis of human OSCC. Our mouth floor model should facillitate the understanding of the molecular pathogenesis of cervical nodal metastasis of OSCC.

• Journal of Gastric Cancer
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• v.1 no.1
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• pp.32-37
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• 2001

Purpose: Three subgroups of stage II stomach cancer (T1N2M0, T2N1M0, T3N0M0) by UICC-TNM staging system show obvious survival difference to each other, which becomes the pitfall of the current staging system. We analyzed the survival and relapse pattern of stage II stomach cancer patients in three subgroups retrospectively to prove the need for change in staging system. Materials and Methods: From July 1989 to December 1995, curative gastric resection was performed in 1,037 patients with gastric adenocarcinoma, and among them 268 patients ($26\%$) were in stage II. The number in each of subgroups (T1N2M0, T2N1M0, and T3N0M0) were 17, 139 and 112 respectively. Survival and relapse pattern were analyzed and median follow up period was 46 months. Results: The 3-year cumulative survival rates of T1N2M0, T2N1M0, and T3N0M0 were $50\%,\;80\%,\;and\;76\%$ respectively (p=0.001). And the 3-year cumulative survival rates of T1N2M0 was comparable to those of 2 subgroups of stage IIIa (T2N2M0, T3N1M0), $47\%\;and\;45\%$ (p>0.05). Peritoneal recurrence was the most frequent in T3N0M0. And hematogenous spread was more frequent in T2N1M0 while nodal spread was more frequent in T1N2M0. Ten out of 17 cases of T1N2M0 died of recurrence. Most of them showed submucosal tumor with depressed lesion and mean tumor size was 3.3 cm. Conclusions: Up-staging of T1N2M0 should be considered because it has the lowest survival rate and the worst prognosis among the three subgroups of Stage II stomach cancer patients. In early gastric cancer patients with high-risk factors (large tumor size, invasion into the submucosal layer, and lymphatic vessel involvement), lymph node dissection and postoperative adjuvant therapy is recommended in an attempt to prevent recurrence in the form of lymph node metastasis.

• Korean Journal of Acupuncture
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• v.27 no.3
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• pp.129-142
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• 2010

Background : The Bonghan theory is a hypothesis on the anatomical structure of the acupuncture point and meridian system. It has been regarded as a misunderstanding of the lymphatic system, or as a made-up story, for the past 40 years. Since 2002, Many studies have been published either to support the theory or to refute the old viewpoint. Objective : The purpose of this study was to find out the validity of the refutation by reviewing the publications. Methods : Searches were made from online databases (Riss4u.net, Google.com, Sciencedirect.com, Pubmed.com, baidu.com, and ci.nii.ac.jp) from 1960 to 2009. The search terms that were used were "Bonghan," "Bong han," "봉한," "thread-like structure," "KИM БOH XaHOM", "CИCTEMA KEHPAK," "鳳漢," "鳳漢管," and "鳳漢学說." References from the searched publications were also used. Results : Since the 1960s, 107 publications were identified as related works, but only 11 publications sought to refute the Bonghan theory. Two publications were researches, and nine were reviews. In the analysis of the correlation of the arguments with the publication contents, it was found that the research of G. Kellner reviewed the Bonghan system properly but that V. V. Kosmatov did not classify the ear-reflex zone as a traditional acupuncture point. For the review publications, only two reviews contained proper arguments, but seven publications were identified as broad interpretations, wrong translations, etc. Moreover, the two proper reviews were grounded on the research of G. Kellner. Conclusions : We found that the scientific origin of the refutation of the Bonghan theory is only one research by G. Kellner. This result suggest that Bonghan theory was not discussed enough to determine the invention.